As indicated in the PA-05-143, one of the main objectives of the Mentored Patient-Oriented Career Development Award (K23) is to increase the pool of clinical researchers able to translate discoveries from basic biomedical research into clinical treatment. The studies described in the present application are designed to allow the candidate to expand his training in treatment research for comorbid alcohol dependence and bipolar disorder. Alcohol dependence is extremely common in individuals with bipolar disorder and has a significant negative impact on the course of bipolar illness. Few treatment studies exist to guide the treatment of alcohol dependence in this comorbid population. Emerging evidence suggests that alterations of glutamate neurotransmission may contribute to both alcohol dependence and bipolar disorder. Lamotrigine, an anticonvulsant medication with known actions at the glutamate synapse, is approved for the treatment of bipolar disorder and has been shown to reduce drinking in a preliminary study of alcohol- dependent persons with comorbid bipolar disorder. Lamotrigine also has been associated with improved neurocognitive functioning in bipolar disorder. The cognitive effects of lamotrigine in individuals with both alcohol dependence and bipolar disorder are unknown. The studies proposed in this application will evaluate the efficacy of lamotrigine on drinking, mood, and neurocognitive outcomes in alcohol-dependent persons with bipolar disorder. During the award period, the candidate will undergo intensive training in (1) the neurobiology of alcoholism and bipolar disorder, 2) advanced clinical trials methodology as it relates to assessment of pharmacotherapies for comorbid alcohol dependence and bipolar disorder, 3) the assessment of neurocognition in individuals with alcohol dependence and/or bipolar disorder for incorporation of this important measure into future treatment trials, 4) the knowledge and skills necessary to successfully apply for independent funding in patient-oriented alcohol research, and 5) research ethics and good research practice. The proposed studies are central to the K.23 career development training plan to develop an independent patient-oriented research program focused on improving the treatment of alcoholism and severe mental illness. PUBLIC HEALTH RELEVANCE: The proposed studies are designed to test whether the medication lamotrigine may help reduce drinking and improve mood stability in alcohol-dependent persons with bipolar disorder. The studies will also test whether the medication lamotrigine may improve cognitive deficits in alcohol-dependent persons with bipolar disorder.